Parmbsc1: a refined force field for DNA simulations

We present parmbsc1, a force field for DNA atomistic simulation, which has been parameterized from high-level quantum mechanical data and tested for nearly 100 systems (representing a total simulation time of ~140 μs) covering most of DNA structural space. Parmbsc1 provides high-quality results in diverse systems. Parameters and trajectories are available at http://mmb.irbbarcelona.org/ParmBSC1/

Assessing control of postural stability in community-living older adults using performance-based limits of stability

<p>Abstract</p> <p>Background</p> <p>Balance disability measurements routinely used to identify fall risks in frail populations have limited value in the early detection of postural stability deficits in community-living older adults. The objectives of the study were to 1) measure performance-based limits of stability (LOS) in community-living older adults and compare them to theoretical LOS computed from data proposed by the Balance Master^®system, 2) explore the feasibility of a new measurement approach based on the assessment of postural stability during weight-shifting tasks at performance-based LOS, 3) quantify intra-session performance variability during multiple trials using the performance-based LOS paradigm.</p> <p>Methods</p> <p>Twenty-four healthy community-living older adults (10 men, 14 women) aged between 62 to 85 (mean age ± sd, 71.5 ± 6 yrs) participated in the study. Subjects' performance-based LOS were established by asking them to transfer their body weight as far as possible in three directions (forward, right and left) without changing their base of support. LOS were computed as the maximal excursion of the COP in each direction among three trials. Participants then performed two experimental tasks that consisted in controlling, with the assistance of visual feedback, their centre of pressure (COP) within two predefined targets set at 100% of their performance-based LOS. For each tasks 8 trials were performed. Ground reaction forces and torques during performance-based LOS evaluation and experimental tasks were recorded with a force plate. Sway area and medio-lateral mean COP displacement speed variables were extracted from force plate recordings.</p> <p>Results</p> <p>Significant differences between theoretical LOS computed from maximum leaning angles derived from anthropometric characteristics and performance-based LOS were observed. Results showed that a motor learning effect was present as the participants optimized their weight-shifting strategy through the first three trials of each task using the visual biofeedback provided on their COP. Reliable measures of control of postural stability at performance-based LOS can be obtained after two additional trials after the learning phase (0.69 > ICC > 1.0).</p> <p>Conclusion</p> <p>Establishing performance-based LOS instead of relying on estimations of theoretical LOS offers a more individualized and realistic insight on the true LOS of an individual. Performance-based LOS can be used as targets during weight-shifting postural tasks with real time visual feedback of the COP displacement to assess postural stability of community-living older adults. In order to obtain reliable results, a learning phase allowing subjects to learn how to control their COP displacement is needed.</p

Using Entropy Maximization to Understand the Determinants of Structural Dynamics beyond Native Contact Topology

Comparison of elastic network model predictions with experimental data has provided important insights on the dominant role of the network of inter-residue contacts in defining the global dynamics of proteins. Most of these studies have focused on interpreting the mean-square fluctuations of residues, or deriving the most collective, or softest, modes of motions that are known to be insensitive to structural and energetic details. However, with increasing structural data, we are in a position to perform a more critical assessment of the structure-dynamics relations in proteins, and gain a deeper understanding of the major determinants of not only the mean-square fluctuations and lowest frequency modes, but the covariance or the cross-correlations between residue fluctuations and the shapes of higher modes. A systematic study of a large set of NMR-determined proteins is analyzed using a novel method based on entropy maximization to demonstrate that the next level of refinement in the elastic network model description of proteins ought to take into consideration properties such as contact order (or sequential separation between contacting residues) and the secondary structure types of the interacting residues, whereas the types of amino acids do not play a critical role. Most importantly, an optimal description of observed cross-correlations requires the inclusion of destabilizing, as opposed to exclusively stabilizing, interactions, stipulating the functional significance of local frustration in imparting native-like dynamics. This study provides us with a deeper understanding of the structural basis of experimentally observed behavior, and opens the way to the development of more accurate models for exploring protein dynamics

Parasite-insecticide interactions: a case study of Nosema ceranae and fipronil synergy on honeybee

In ecosystems, a variety of biological, chemical and physical stressors may act in combination to induce illness in populations of living organisms. While recent surveys reported that parasite-insecticide interactions can synergistically and negatively affect honeybee survival, the importance of sequence in exposure to stressors has hardly received any attention. In this work, Western honeybees (Apis mellifera) were sequentially or simultaneously infected by the microsporidian parasite Nosema ceranae and chronically exposed to a sublethal dose of the insecticide fipronil, respectively chosen as biological and chemical stressors. Interestingly, every combination tested led to a synergistic effect on honeybee survival, with the most significant impacts when stressors were applied at the emergence of honeybees. Our study presents significant outcomes on beekeeping management but also points out the potential risks incurred by any living organism frequently exposed to both pathogens and insecticides in their habitat

The links between health-related behaviors and life satisfaction in elderly individuals who prefer institutional living

BACKGROUND: Life satisfaction among residents of institutions is becoming an important issue in a rapidly aging population. The aim of this cross-sectional study was to investigate the links between life satisfaction and health-related behaviors amongst functionally independent elderly people who prefer institutional living in İstanbul, Turkey. METHODS: The socio-demographic characteristics, health-related behaviors, leisure-time activities and fall histories of 133 residents of an institution in Istanbul were assessed by a structured questionnaire during face-to-face interviews. A validated life-satisfaction index questionnaire (LSI-A) was completed. RESULTS: The mean age of the study group was 73.9 ± 8.0 (range 60–90 years). Within the group, 22.6% had never married and 14.3% had university degrees. The majority (71.4%) were in the low income bracket. The overall mean LSI-A score was 20.3 ± 5.9. Participants who declared moderate/high income levels had a significantly higher mean LSI-A score than those in the low-income bracket (p = 0.009). Multivariate analysis of the data suggested that leisure-time activities and participation in regular physical activities are significant predictors of LSI-A scores (R(2): 0.112; p = 0.005 and p = 0.02, respectively). CONCLUSION: The findings imply that regular physical activity and leisure-time activities are significantly related to life satisfaction among residents in institutions. Participation in physical activity and leisure-time activity programs may help to improve the life satisfaction of elderly people living in institutions

Effect of foot orthoses on lower extremity kinetics during running: a systematic literature review

<p>Abstract</p> <p>Background</p> <p>Throughout the period of one year, approximately 50% of recreational runners will sustain an injury that disrupts their training regimen. Foot orthoses have been shown to be clinically effective in the prevention and treatment of several running-related conditions, yet the physical effect of this intervention during running remains poorly understood. The aim of this literature review was therefore to evaluate the effect of foot orthoses on lower extremity forces and pressure (kinetics) during running.</p> <p>Methods</p> <p>A systematic search of electronic databases including Medline (1966-present), CINAHL, SportDiscus, and The Cochrane Library occurred on 7 May 2008. Eligible articles were selected according to pre-determined criteria. Methodological quality was evaluated by use of the Quality Index as described by Downs & Black, followed by critical analysis according to outcome variables.</p> <p>Results</p> <p>The most widely reported kinetic outcomes were loading rate and impact force, however the effect of foot orthoses on these variables remains unclear. In contrast, current evidence suggests that a reduction in the rearfoot inversion moment is the most consistent kinetic effect of foot orthoses during running.</p> <p>Conclusion</p> <p>The findings of this review demonstrate systematic effects that may inform the direction of future research, as further evidence is required to define the mechanism of action of foot orthoses during running. Continuation of research in this field will enable targeting of design parameters towards biomechanical variables that are supported by evidence, and may lead to advancements in clinical efficacy.</p

Understanding the Warburg effect and the prognostic value of stromal caveolin-1 as a marker of a lethal tumor microenvironment

Cancer cells show a broad spectrum of bioenergetic states, with some cells using aerobic glycolysis while others rely on oxidative phosphorylation as their main source of energy. In addition, there is mounting evidence that metabolic coupling occurs in aggressive tumors, between epithelial cancer cells and the stromal compartment, and between well-oxygenated and hypoxic compartments. We recently showed that oxidative stress in the tumor stroma, due to aerobic glycolysis and mitochondrial dysfunction, is important for cancer cell mutagenesis and tumor progression. More specifically , increased autophagy/mitophagy in the tumor stroma drives a form of parasitic epithelial-stromal metabolic coupling. These findings explain why it is effective to treat tumors with either inducers or inhibitors of autophagy, as both would disrupt this energetic coupling. We also discuss evidence that glutamine addiction in cancer cells produces ammonia via oxidative mitochondrial metabolism. Ammonia production in cancer cells, in turn, could then help maintain autophagy in the tumor stromal compartment. In this vicious cycle, the initial glutamine provided to cancer cells would be produced by autophagy in the tumor stroma. Thus, we believe that parasitic epithelial-stromal metabolic coupling has important implications for cancer diagnosis and therapy, for example, in designing novel metabolic imaging techniques and establishing new targeted therapies. In direct support of this notion, we identified a loss of stromal caveolin-1 as a marker of oxidative stress, hypoxia, and autophagy in the tumor microenvironment, explaining its powerful predictive value. Loss of stromal caveolin-1 in breast cancers is associated with early tumor recurrence, metastasis, and drug resistance, leading to poor clinical outcome